Nanomaterials quickly evolve to produce safe and effective biomedical alternatives, mainly silver nanoparticles (AgNPs). The AgNPs’ antibacterial, antiviral, and antitumor properties convert them into a recurrent scaffold to produce new treatment options. This work reported the full characterization of a highly biocompatible protein-coated AgNPs formulation and their selective antitumor and amoebicidal activity. The protein-coated AgNPs formulation exhibits a half-inhibitory concentration (IC₅₀) = 19.7 µM (2.3 µg/mL) that is almost 10 times more potent than carboplatin (first-line chemotherapeutic agent) to inhibit the proliferation of the highly aggressive human adenocarcinoma HCT-15. The main death pathway elicited by AgNPs on HCT-15 is apoptosis, which is probably stimulated by reactive oxygen species (ROS) overproduction on mitochondria. A concentration of 111 µM (600 µg/mL) of metallic silver contained in AgNPs produces neither cytotoxic nor genotoxic damage on human peripheral blood lymphocytes. Thus, the AgNPs formulation evaluated in this work improves both the antiproliferative potency on HCT-15 cultures and cytotoxic selectivity ten times more than carboplatin. A similar mechanism is suggested for the antiproliferative activity observed on HM1-IMSS trophozoites (IC₅₀ = 69.2 µM; 7.4 µg/mL). There is no change in cell viability on mice primary cultures of brain, liver, spleen, and kidney exposed to an AgNPs concentration range from 5.5 µM to 5.5 mM (0.6 to 600 µg/mL). The lethal dose was determined following the OECD guideline 420 for Acute Oral Toxicity Assay, obtaining an LD₅₀ = 2618 mg of Ag/Kg body weight. All mice survived the observational period; the histopathology and biochemical analysis show no differences compared with the negative control group. In summary, all results from toxicological evaluation suggest a Category 5 (practically nontoxic) of the Globally Harmonized System of Classification and Labelling of Chemicals for that protein-coated AgNPs after oral administration for a short period and urge the completion of its preclinical toxicological profile. These findings open new opportunities in the development of selective, safe, and effective AgNPs formulations for the treatment of cancer and parasitic diseases with a significant reduction of side effects.

中文翻译：

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新型蛋白包被的银纳米颗粒：表征，抗肿瘤和杀螨活性，抗增殖选择性，基因毒性和生物相容性评估

纳米材料迅速发展为生产安全有效的生物医学替代品，主要是银纳米颗粒（AgNPs）。AgNPs的抗菌，抗病毒和抗肿瘤特性将其转变为复发支架，从而产生了新的治疗选择。这项工作报告了高度生物相容性蛋白包被的AgNPs制剂的全面表征及其选择性的抗肿瘤和杀螨活性。蛋白质包被的AgNPs制剂表现出半抑制浓度（IC ₅₀）= 19.7 µM（2.3 µg / mL），几乎比卡铂（一线化疗剂）抑制强侵袭性人类腺癌HCT-15增殖的效力高10倍。AgNPs在HCT-15上引发的主要死亡途径是细胞凋亡，这可能是由线粒体上的活性氧（ROS）过量产生刺激的。AgNP中所含金属银的浓度为111 µM（600 µg / mL），不会对人体外周血淋巴细胞产生细胞毒性或遗传毒性。因此，这项工作中评估的AgNPs配方可提高对HCT-15培养物的抗增殖能力和细胞毒性选择性，是卡铂的十倍。对于HM1-IMSS滋养体观察到的抗增殖活性也提出了类似的机制（IC ₅₀= 69.2 µM；7.4微克/毫升）。在暴露于5.5 µM至5.5 mM（0.6至600 µg / mL）的AgNPs浓度的小鼠的大脑，肝脏，脾脏和肾脏的原代培养物中，细胞活力没有变化。按照OECD准则420进行的急性口服毒性测定确定致死剂量，得出LD ₅₀= 2618 mg Ag / Kg体重。所有小鼠在观察期内均存活。组织学和生化分析与阴性对照组相比无差异。总而言之，毒理学评估的所有结果都表明，口服这种蛋白质涂层的AgNPs的短时间口服后，全球化学品统一分类和标签制度第5类（实际上无毒），并敦促完成其临床前毒理学分析。这些发现为开发选择性，安全和有效的AgNPs制剂提供了新的机遇，这些制剂可用于治疗癌症和寄生虫病，且副作用显着减少。